Exploring Causal Correlations Between Depression and Musculoskeletal Disorders: A Bidirectional Mendelian Randomization Study

OBJECTIVE: Observational studies suggest a strong but poorly understood association between depression and musculoskeletal disorders (MSDs). This study aims to investigate the bidirectional causal relationships between depression and specific MSDs using Mendelian randomization (MR). METHODS: Bidirectional MR used GWAS data from European (n=484,598) and East Asian (n=152,389) populations. Independent SNPs ( P <5×10 - ⁸; supplementary P <1×10 - ⁷; F>10) were IVs. Causal effects were estimated via inverse variance weighted (IVW), MR-RAPS, and other methods, with sensitivity tests (MR-PRESSO, stratified analysis) for pleiotropy/heterogeneity. RESULTS: Genetically predicted depression was associated with increased risk of neck-shoulder pain (IVW OR 1.48, 95%CI 1.26-1.71, P =7.14×10 - ⁶), hip pain (OR 1.20, 95%CI 1.05-1.37, P =0.005), and knee pain (OR 1.29, 95%CI 1.09-1.52, P =0.002), but not back or low back pain. Reverse MR indicated significant effects of neck-shoulder pain (OR 1.08, 95%CI 1.05-1.12, P =6.22×10 - ⁷), back pain (OR 1.00, 95%CI 0.99-1.00, P =1.18×10 - ¹¹), hip pain (OR 1.06, 95%CI 1.01-1.12, P =0.014), and knee pain (OR 1.02, 95%CI 1.00-1.05, P =0.025) on depression risk. No significant heterogeneity or horizontal pleiotropy was detected in most analyses, though some reverse analyses showed evidence of these violations. CONCLUSIONS: Genetic prediction of depression correlates with increased neck-shoulder/hip/knee pain risk, with reverse associations for these MSDs and depression. Findings are preliminary and require clinical validation.